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MHC Complexes (mhc + complex)
Selected AbstractsPeptide-,2-microglobulin-major histocompatibility complex expressing cells are potent antigen-presenting cells that can generate specific T cellsIMMUNOLOGY, Issue 1 2007Sonja Obermann Summary Adoptive T-cell therapy represents a promising therapeutic approach for the treatment of cancer. Successful adoptive immunotherapy depends on the ex vivo priming and expansion of antigen-specific T cells. However, the in vitro generation of adequate numbers of functional antigen-specific T cell remains a major obstacle. It is important to develop efficient and reproducible methods to generate high numbers of antigen-specific T cells for adoptive T-cell transfer. We have developed a new artificial antigen-presenting cell (aAPC) by transfection of major histocompatibility (MHC) class I negative Daudi cells with a peptide-,2-microglobulin,MHC fusion construct (single-chain aAPC) ensuring presentation of the peptide,MHC complex of interest. Using this artificial antigen-presenting cell, we could generate up to 9·2 × 108 antigen-specific cytotoxic CD8+ T cells from 10 ml blood. In vitro generated T cells lysed endogenously presented antigens. Direct comparison of the single-chain aAPC with autologous monocyte-derived dendritic cells demonstrated that these cells were equally efficient in stimulation of T cells. Finally, we were able to generate antigen-specific T cell lines from perpheral blood mononuclear cells of patients receiving cytotoxic chemotherapy. The use of single-chain aAPC represent a promising option for the generation of antigen-specific CD8+ T cells, which could be used for adoptive T-cell therapy. [source] A preliminary study of possible genetic influences on the susceptibility of sheep to Johne's diseaseAUSTRALIAN VETERINARY JOURNAL, Issue 7 2005LA REDDACLIFF Objective To investigate possible genetic influences on susceptibility or resistance of sheep to Johne's disease. Design A field and laboratory study of two fine-wool Merino flocks with a high prevalence of disease due to Mycobacterium avium subsp paratuberculosis infection. Procedure Adult sheep were phenotypically classified as having severe, mild or no disease on the basis of clinical, pathological and cultural tests for paratuberculosis, and as positive or negative in tests for humoral immunity (agar gel immunodiffusion test) or cell mediated immunity (skin test for delayed type hyper-sensitivity). Correlations with phenotype were sought for polymorphisms at loci within selected immune function genes (NRAMP, MHC complex, IFN-,, lysozyme, leukaemia inhibiting factor). Results Possible associations of particular NRAMP and MHC alleles with susceptibility or resistance to Johne's disease were detected. Conclusion If the results of this preliminary study are confirmed in further work, then the use of rams with "resistant" genotypes may assist in the control of Johne's disease in infected flocks. [source] Signalling and phagocytosis in the orchestration of host defenceCELLULAR MICROBIOLOGY, Issue 2 2007J. Magarian Blander Summary Dendritic cells (DCs) orchestrate either tolerance or immunity. At the heart of this function lies phagocytosis, which allows DCs to sample the tissue microenvironment and deliver both its self and non-self constituents into endocytic compartments for clearance, degradation and presentation by major histocompatibility complex (MHC) molecules. Depending on the type of signalling pathways triggered during phagocytosis, DCs deliver appropriate signals to T cells that determine either their tolerance or activation and differentiation. Here I draw attention to the ability of DCs to read the contents of their phagosomes depending on the type of compartmentalized signalling pathways engaged during internalization. Toll-like receptors (TLRs) engaged during phagocytosis of microbial pathogens, but not syngeneic apoptotic cells exert phagosome autonomous control on both the kinetics and outcome of phagosome maturation. By bearing the assembly of signalling complexes on their membranes, individual phagosomes undergo separate programmes of maturation irrespective of the activation status of the DC carrying them. Phagosomes carrying microbial cargo are favoured for MHC class II presentation precluding phagosomes carrying self from contributing to the first signal delivered to T cells , the peptide,MHC complex. This mechanism prevents the potential presentation of peptides derived from self within the context of TLR-induced co-stimulatory signals. [source] Antigen-loaded ER microsomes from APC induce potent immune responses against viral infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2009Vassiliki Sofra Abstract Although matured DC are capable of inducing effective primary and secondary immune responses in vivo, it is difficult to control the maturation and antigen loading in vitro. In this study, we show that ER-enriched microsomal membranes (microsomes) isolated from DC contain more peptide-receptive MHC I and II molecules than, and a similar level of costimulatory molecules to, their parental DC. After loading with defined antigenic peptides, the microsomes deliver antigenic peptide,MHC complexes (pMHC) to both CD4 and CD8 T cells effectively in vivo. The peptide-loaded microsomes accumulate in peripheral lymphoid organs and induce stronger immune responses than peptide-pulsed DC. The microsomal vaccines protect against acute viral infection. Our data demonstrate that peptide,MHC complexes armed microsomes from DC can be an important alternative to DC-based vaccines for protection from viral infection. [source] Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2003Laurence Ardouin Abstract Activation of T lineage cells through the TCR by peptide,MHC complexes on APC is critically dependent on rearrangement of the actin cytoskeleton. Vav1 is a guanine nucleotide exchange factor for members of the Rho/Rac family of GTPases which is activated following TCR stimulation, suggesting that it may transduce TCR signals to the activation of some or all actin-controlled processes. Weshow that Vav1-deficient double-positive thymocytes are less efficient at forming conjugates with APC presenting agonist peptide than wild-type cells are. Furthermore we demonstrate that Vav1 is required for TCR-induced activation of the integrin LFA-1, which is likely to explain the defect in conjugate formation. However, once Vav1-deficient cells form a conjugate, the assembly of proteins into an immunological synapse at the conjugate interface is normal. In contrast, thymocyte polarization is defective in the absence of Vav1, as judged by the relocalization of the microtubule-organizing center. These data demonstrate that Vav1 transduces signals to only a subset of cytoskeleton-dependent events at the immunological synapse. [source] Disparate peptide-dependent thymic selection outcomes in ,2M-deficient mice versus TAP-1-deficient mice: implications for repertoire formationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2003Tetsuro Sasada Abstract Fetal thymic organ cultures of N15-transgenic RAG-2,/, H-2b mice on normal, ,-2 microglobulin (,2M),/, or transporter associated with antigen processing (TAP-1),/, MHCI-deficient backgrounds were used to examine differentiation of thymocytes bearing a TCR specific for a viral peptide bound to H-2Kb. Strong agonists mediate negative selection in all mice whereas weak agonists are positively selecting in ,2M,/, mice but negatively selecting on TAP-1,/, or normal backgrounds. Very weak agonists and very weak antagonists are generally without effect in ,2M,/, mice yet foster differentiation in TAP-1,/, animals. The 20,40-fold reduction in ,2M,/, thymic H-2Kb surface expression suggests that the avidity of the TCR for peptide,MHCI accounts for these differences, consistent with effects of TCR density and individual thymic-peptide abundance in peptide,MHC complexes. TCR,self-MHC interaction dominates Kb -based selection, subtly modulated by peptides as revealed by X-ray crystallography. [source] Regulatory T cells and autoimmune diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2005Silke Paust Summary:, Although T-cell clones bearing T-cell receptors with high affinity for self-peptide major histocompatibility complex (MHC) products are generally eliminated in the thymus (recessive tolerance), the peripheral T-cell repertoire remains strongly biased toward self-peptide MHC complexes and includes autoreactive T cells. A search for peripheral T cells that might exert dominant inhibitory effects on autoreactivity has implicated a subpopulation of CD4+CD25+ T cells called regulatory T cells (Tregs). Here, we discuss the role of cytokines and costimulatory molecules in the generation, maintenance, and function of Tregs. We also summarize evidence for the involvement of Tregs in controlling autoimmune diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and inflammatory bowel disease. Last, we discuss our recent definition of the potential role of B7 expressed on activated T-effector cells as a target molecule for Treg-dependent suppression. These observations suggest that the engagement of B7 on effector T cells transmits an inhibitory signal that blocks or attenuates effector T-cell function. We restrict our comments to the suppression mediated by cells within the CD4 lineage; the impact of the cells within the CD8 lineage that may suppress via engagement of Qa-1 on effector T cells is not addressed in this review. [source] Non-natural CBP2 binding peptides and peptomers modulate carcinoma cell adhesion and invasionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2001Carla Hebert Abstract A combinatorial approach that utilized a repertoire of bacteriophage-peptides has identified a number of non-natural CBP2 binding peptides. Moreover, co-localization of some of these peptides with CBP2 in a number of tumor cell lines demonstrated that the peptides were directed to an intracellular location spatially coincident with the normal distribution of CBP2 [Sauk et al., 2000]. From among these sequences WHYPWFQNWAMA and LDSRYSLQAAMY were the most effective CBP2 binding peptides and best fulfilled the combinatorial motif containing deep hydrophobic pockets. When the hydropathic profiles of collagen ,1(IV) and ,2 (IV) were compared with these dodecapeptides, the hydropathic profiles of WHYPWFQNWAMA and LDSRYSLQAAMY closely matched those of ,1(IV) 414,452 and ,1(IV)531,543. These peptides were shown to be functional peptidomimics and possessed the ability to alter cell adhesion and invasion of human squamous cell carcinoma cell lines. Peptomers were formed of these non-natural peptides to explore the role that a repetitive peptide may have on cell adhesion. The enhanced cell adhesion observed with the peptomers required both CBP2 antibodies and integrin antibodies for inhibition. The enhanced adhesion observed even in the face of combined antibody inhibition was consistent with such complexes possessing correspondingly slower dissociation rates. Thus, suggesting that peptomers may function in a like manner to multimeric peptide MHC complexes (tetramers) binding more than one cell receptor on a specific cell. These findings evoke both peptidomimics of native ligands and their peptomers as potential reagents by which to target tumor cells for chemotherapy, imaging, or retargeting viral vectors for gene therapy. J. Cell. Biochem. 82: 145,154, 2001. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||